Structure and sequence variation of mink interleukin-6 gene

Aleutian disease (AD) is the number one disease threat to the survival and future of the mink industry in Nova Scotia and the world. Several ranchers have gone out of business in recent years in Nova Scotia as a direct result of AD. Currently, the control measure for AD consists of testing and slaughtering of infected mink. This practice has not been effective in controlling the disease. Finding a means of controlling AD is the number one priority for the mink industry in Nova Scotia. An effective control measure will have a long-term positive effect on the rural economy by improving production potential of mink and reducing production cost. It has been shown that antiviral antibodies produced by activated immune system cells sometimes combine with interleukin-6 (IL-6) to form immune complexes that cause AD in mink. There is evidence of a significant relationship between nucleotide variations in IL-6 gene and the onset of certain diseases in humans, which bears similar symptoms to AD. Furthermore, pathological symptoms of AD resemble those of other conditions, such as systemic lupus erythematosus (SLE) and Castleman Diseases in humans, where overproduction of IL-6 coincides with the severity of the disease. These findings suggest that IL-6 could be a candidate gene and warrant investigation vis-a-vis differences among mink genotypes in resistance or tolerance to ADV infection. The sequence of the IL-6 gene in mink was done and identification of polymorphisms was used to evaluate the potential role of this gene in the immune system response to infections. The 4678 bp promoter region, five exons and four introns of the interleukin-6 (IL-6) gene were bi-directionally sequenced in four unrelated mink from each of the wild, black, brown, pastel and sapphire mink (Genbank accession number (EF620932). The 344 bp promoter region of the gene contained several transcription binding sites. One exonic and seven intronic single nucleotide polymorphisms (SNP) were detected by sequencing of the 20 mink and genotyping of an additional 82 animals from the five colour types. Only two intronic SNP were segregating at high frequencies, indicating that the level of polymorphisms in the mink IL-6 gene was low. A bi-allelic tetranucleotide repeat was detected in the promoter region, with the frequency of 0.0, 0.17, 0.25, 0.25 and 0.40 in the wild, black, pastel, brown and sapphire mink, respectively, suggesting that this locus may influence immune response to infection. A polymorphic (CA)16 with 10 alleles was also detected in intron 2. (author)